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The incidence of Parkinson's disease (PD) rises rapidly with the increase of age. With the advent of global aging, the number of patients with PD is rising along with the elderly population, especially in China. Previously, we found that Yishen chuchan decoction (YCD), prescribed based on clinical experience, has the potential of alleviating symptoms, delaying the progression, and controlling the development of PD. Nonetheless, the underlying mechanistic role is yet to be explored. Aim: This research examined the possible therapeutic effects of YCD in alleviating PD via a systematic approach with network pharmacology and experimental validation, aiming at providing a new understanding of traditional Chinese medicine management regarding PD. Methods: The chemical structure and properties of YCD were adopted from Traditional Chinese Medicine System Pharmacology Database (TCMSP), SwissADME, PubChem, and PubMed. The potential targets for YCD and PD were identified using Swiss Target Prediction, GeneCard, PubChem, and UniProt. The herbal-component-target network was created via the Cytoscape software. Moreover, by using the STRING database, the protein-protein interaction (PPI) network was screened. Gene function GO and KEGG pathway enrichment analyses were performed via the Metascape database. YCD-medicated Rat Serum from Sprague-Dawley (SD) Rats was prepared, and SH-SY5Y cells were preconditioned with rotenone to develop the PD model. To examine the impact of YCD on these cells and explore the mechanistic role of the p38 mitogen-activated protein kinase (MAPK) pathway, the cells were pretreated with either serum or a p38 MAPK pathway inhibitor. This study employed the Cell Counting Kit (CCK)-8 assay and Hoechst 33,342 staining to evaluate the viability and morphological changes induced by the YCD-medicated rat serum on rotenone-treated SH-SY5Y cells. Apoptosis was assessed by Flow cytometry. Immunofluorescence staining assessed the microtubule-associated protein 2 (MAP2) level. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the concentrations of inflammatory mediators interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Also, reactive oxygen species (ROS) and superoxide dismutase (SOD) levels were determined. Western Blotting measured the expression of total and phospho-p38 MAPK (p-p38). Results: This study identified 65 active components in YCD, which were found to target 801 specific genes. By screening, 63 potential core targets were identified from a pool of 172 overlapping targets between PD and YCD. These targets were examined by GO and KEGG analyses revealing their substantial correlation to MAPK, PI3K-Akt signaling pathways, positively controlling protein phosphorylation, and pathways of neurodegenerative diseases. SH-SY5Y cells were treated with 2 µM rotenone for 48 h, which reduced cell viability to 50 %, and reduced MAP2 expression, increased the rate of apoptosis, oxidative stress, inflammation, and p-p38 expressions. YCD-medicated rat serum significantly improved the viability, reduced the apoptosis rate, and increased the MAP2 expression. YCD-medicated serum increased SOD, reduced ROS and suppressed IL-6, IL-1ß and TNF-α levels, thus inhibiting oxidative stress and inflammation in rotenone-treated SH-SY5Y cells. Moreover, YCD-medicated serum substantially lowered the p-p38 expression induced by rotenone. SB203580, a specific inhibitor of p38 MAPK, could also inhibit the p-p38 expression, apoptosis, and restore morphological damage of cells, also improve inflammation and oxidative stress. Conclusion: YCD enhanced cell viability and reduced apoptosis rate, inflammation, and oxidative stress in vitro. These beneficial effects could potentially involve the suppression of p38 pathway and suppressed the phosphorylation of p38 MAPK.
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ETHNOPHARMACOLOGICAL RELEVANCE: Treating cognitive impairment is a challenging and necessary research topic. ZeXieYin Formula (ZXYF), is a traditional herbal formula documented in the book of HuangDiNeiJing. Our previous studies demonstrated the ameliorative effects of ZXYF on atherosclerosis by reducing the plasma trimethylamine oxide (TMAO) level. TMAO is a metabolite of gut microorganisms, our recent research found that the increasing level of TMAO may have adverse effects on cognitive functions. AIM OF THE STUDY: Our study mainly focused on the therapeutic effects of ZXYF on TMAO-induced cognitive impairment in mice and explored its underlying mechanism. MATERIALS AND METHODS: After the TMAO-induced cognitive impairment mice models were established, we applied behavioral tests to estimate the learning and memory ability of the ZXYF intervention mice. Liquid chromatography-mass spectrometry (LC-MS) was used to quantify the TMAO levels in plasma and the brain. The effects of ZXYF on the hippocampal synaptic structure and the neurons were observed by transmission electron microscopy (TEM) and Nissl staining. In addition, western-blotting (WB) and immunohistochemical (IHC) staining were used to detect the level of related proteins in the synaptic structure and further verify the changes in synaptic plasticity and the mTOR pathway after ZXYF administration. RESULTS: Behavioral tests showed that the learning and memory ability of mice impaired after a period of TMAO intervention and ZXYF could alleviate these changes. A series of results showed that ZXYF partly restored the damage of hippocampal synapse and neurons in TMAO-induced mice, at the same time, the expression of synapse-related proteins and mTOR pathway-related proteins were significantly regulated compared with the damage caused by TMAO. CONCLUSION: ZXYF could alleviate TMAO-induced cognitive impairment by improving synaptic function, reducing neuronal damage, regulating synapse-associated proteins, and regulating the mTOR signaling pathway.
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Disfunção Cognitiva , Aprendizagem , Camundongos , Animais , Plasticidade Neuronal , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Serina-Treonina Quinases TORRESUMO
Mild cognitive impairment (MCI) is an intermediate state between "healthy" and "dementia", which affects memory and cognitive function. Timely intervention and treatment of MCI can effectively prevent it from developing into an incurable neurodegenerative disease. Lifestyle factors, such as dietary habits, were highlighted as risk factors for MCI. The effect of a high-choline diet on cognitive function is contentious. In this study, we focus our attention on the choline metabolite trimethylamine-oxide (TMAO), an acknowledged pathogenic molecule of cardiovascular disease (CVD). With recent studies indicating that TMAO also plays a potential role in the central nervous system (CNS), we aim to explore the effect of TMAO on synaptic plasticity in the hippocampus, the basic structure of studying and memory. Using various hippocampal-dependent spatial references or working memory-related behavioral texts, we found that TMAO treatment caused both long-term memory (LTM) and short-term memory (STM) deficits in vivo. Simultaneously, the plasm and whole brain levels of choline and TMAO were measured by employing liquid phase mass spectrometry (LC/MS). Furthermore, the effects of TMAO on the hippocampus were further explored by applying Nissl staining and transmission electron microscopy (TEM). Moreover, the expression of synaptic plasticity-related proteins, including synaptophysin (SYN), postsynaptic density protein95 (PSD95), and N-methyl-aspartate receptor (NMDAR), was examined by western blotting and immunohistochemical (IHC). The results showed that TMAO treatment contributes to neuron loss, synapse ultrastructure alteration, and synaptic plasticity impairments. In mechanism, the mammalian target of rapamycin (mTOR) regulates synaptic function, and the activation of the mTOR signaling pathway was observed in TMAO groups. In conclusion, this study confirmed that the choline metabolite TMAO can induce hippocampal-dependent learning and memory ability impairment with synaptic plasticity deficits by activating the mTOR signaling pathway. The effects of choline metabolites on cognitive function may provide a theoretical basis for establishing the daily reference intakes (DRIs) of choline.
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Doenças Neurodegenerativas , Proteínas Quinases S6 Ribossômicas 70-kDa , Humanos , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Doenças Neurodegenerativas/metabolismo , Cognição , Plasticidade Neuronal , Dieta , Metilaminas/metabolismo , Colina/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Hipocampo/metabolismoRESUMO
Since student L2 achievement is the primary objective of all language education contexts, a huge number of inquiries have explored the role of students' personal characteristics in promoting their L2 achievement. A plethora of studies have also assessed the impact of teachers' personal and professional qualities on students' L2 achievement. Yet, the effects of teachers' organizational commitment and loving pedagogy have largely been neglected. In addition, no review article has been undertaken to outline the consequences of teachers' organizational commitment and loving pedagogy for students' L2 achievement. Against this backdrop, the present article intends to describe the role of teachers' organizational commitment and loving pedagogy in EFL students' L2 achievement by reviewing the theoretical and empirical evidence. The review revealed that teachers' organizational commitment and loving pedagogy can favorably influence EFL students' L2 achievement. The implications for language teachers, teacher trainers, and educational administrators are also discussed.
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Atherosclerosis is the main cause of cardiovascular diseases. The Fat-1 gene can express the n-3 fatty acid desaturase, which converts n-6 polyunsaturated fatty acids (PUFA) to n-3 PUFAs. The role of n-3 PUFAs in atherosclerosis is widely debated. This study explored the effect of n-3 PUFAs on atherosclerosis in rabbits. In this study, atherosclerosis was induced in Fat-1 transgenic rabbits and their littermate (WT) rabbits by feeding a high-cholesterol diet containing 0.3% cholesterol and 3% soybean oil for 16 weeks. Plasma lipid, fatty acid and pathological analyses of atherosclerotic lesions were conducted. Fatty acid composition in the liver and muscle showed that n-3 PUFAs increased and n-6 PUFAs decreased in the Fat-1 group. Plasma high-density lipoprotein cholesterol (HDL-C) levels were significantly increased in the Fat-1 group, and the atherosclerotic lesion area of the aortic arch in Fat-1 transgenic rabbits was significantly reduced. Histological analysis showed that smooth muscle cells (SMCs) in atherosclerotic lesions decreased significantly. In conclusion, n-3 PUFAs improve atherosclerosis in Fat-1 transgenic rabbits, and this process may depend on the increase in plasma HDL-C and the decrease in the amount of SMCs in atherosclerotic plaques.
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Aterosclerose , Ácidos Graxos Ômega-3 , Hipercolesterolemia , Placa Aterosclerótica , Animais , Aterosclerose/patologia , Ácidos Graxos Ômega-6 , Hipercolesterolemia/patologia , Placa Aterosclerótica/genética , CoelhosRESUMO
RATIONALE: Acute lymphoblastic leukemia (ALL) has acute and severe onset characterized by fever, moderate to severe anemia, bone and joint pain, and sternal tenderness. It is easy to be misdiagnosed as rheumatic disease when joint pain is the first symptom. PATIENT CONCERNS: A male Han, 18 years of age was admitted on July 15th, 2016 for multi-joint swelling and pain with intermittent fever for half a year which had aggravated in the last 10 days. DIAGNOSIS: Based on symptoms, imaging, family history, and blood tests, he was first diagnosed with ankylosing spondylitis, but he was refractory to treatment. Bone marrow biopsy then revealed acute B-lymphoblastic leukemia (possibility Pro-B-ALL). INTERVENTIONS: The patient was transferred to the hematology department on July 23rd, 2016 for chemotherapy. OUTCOMES: No joint pain occurred during follow-up, which ended on November 4th, 2018. LESSONS: ALL may present with symptoms suggestive of rheumatic diseases like ankylosing spondylitis. Physicians should be aware of this possibility, especially in young patients.
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Artralgia/etiologia , Leucemia Linfocítica Crônica de Células B/patologia , Espondilite Anquilosante/diagnóstico , Adolescente , Antineoplásicos/uso terapêutico , Artralgia/diagnóstico , Biópsia , Medula Óssea/patologia , Diagnóstico Diferencial , Erros de Diagnóstico , Febre/diagnóstico , Febre/etiologia , Humanos , Artropatias/diagnóstico por imagem , Artropatias/patologia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Espondilite Anquilosante/sangue , Espondilite Anquilosante/terapia , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
The aim of the present study was to investigate the efficiency and safety of a combination of thalidomide and chemo-radiotherapy (CRT) for treating esophageal cancer (EC). Eligible patients received two cycles of chemotherapy using paclitaxel liposome and cisplatin concurrently with three-dimensional radiotherapy. Following radiotherapy, two cycles of maintenance chemotherapy were performed. Patients with elevation of vascular endothelial growth factor (VEGF) during radiotherapy were randomly divided into: i) a test group (n=31), who received a combination of CRT and thalidomide; and ii) a control group (n=30), who received CRT only. Patients with locally advanced EC in the test group demonstrated a significantly improved 3-year overall survival (OS) rate, progression-free survival (PFS) rate, local control and median PFS time compared with the control group (P<0.05). Multivariate analysis indicated that Tumor-Node-Metastasis (TNM) stage was associated with the OS time, while TNM stage and the residence of cancer cells following radiotherapy were associated with PFS time. The present data indicate that thalidomide contributes to an improvement of prognosis for patients with locally advanced EC with elevated serum VEGF levels during radiotherapy. In addition, the toxicities induced by thalidomide were demonstrated to be tolerable.
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The aim of this study was to observe pathological response and change in serum vascular endothelial growth factor (VEGF) in esophageal carcinoma (EC) during chemoradiotherapy (CRT).Eighty-nine patients diagnosed with EC were treated with radiotherapy at the Department of Radiotherapy of the Second People's Hospital of Changzhou between May 2008 and December 2014, including 65 patients with CRT. Gastroscopy and pathological examination were conducted 4 weeks afterwards. The pathological responses were classified as complete response (CR) and non-CR. Serum samples were collected from the patients before radiotherapy, during week 4 of radiotherapy, and 1 week after radiotherapy. The VEGF changes were classified as increase, stable, and decrease.The median overall survival (OS) and median progression-free survival (PFS) in the pathological CR group was significantly longer than that of the non-CR group (Pâ<â.001). The 1-, 3-, and 5-year OS rates in the non-CR group were lower than that in the CR group (Pâ<â.05). Moreover, the 1-, 3-, and 5-year PFS rates in the non-CR group were lower than that in the CR group (Pâ<â.05). VEGF serum level was decreased during and after radiotherapy compared with pre-radiotherapy, and the differences were statistically significant (Pâ<â.05). The 1-, 3-, and 5-year OS rates in the increased group were lower than that in the decreasing group (Pâ<â.05). Moreover, the 1-, 3-, and 5-year PFS rates in the increasing group were lower than that in the decreasing group (Pâ<â.05). Pathological response (Pâ<â.05), serum VEGF trend (Pâ<â.05), and tumor-node-metastasis stage (Pâ<â.05) in response to CRT were factors that influenced patient prognosis.Pathological response and serum VEGF change during CRT can predict prognosis of nonsurgical patients with EC. Monitoring these changes is of significance in individualized treatment.
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Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Idoso , Biomarcadores Tumorais , Carcinoma de Células Escamosas/mortalidade , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
The aim of this study was to design a lower limb immobilization device and investigate its clinical application in the radiotherapy of the lower limbs.Around 38 patients who underwent lower limb radiotherapy using the designed immobilization device were included in this study. The setup errors were calculated by comparison of the portal images and the simulator films or digital reconstructed radiographs (DRRs).From all 38 patients accomplished the radiotherapy using this device, 178 anteroposterior portal images and 178 lateral portal images were used for the analysis of the positional accuracy. Significant differences were observed in the setup error of the head-foot direction compared with the left-right direction (tâ=â3.404, Pâ=â.002) and the anterior-posterior directions (tâ=â3.188, Pâ=â.003). No statistical differences were identified in the setup error in the left-right direction and anterior-posterior direction (tâ=â0.497, Pâ=â.622).The use of the in-house designed lower limb immobilization device allowed for relatively small setup errors. Furthermore, it showed satisfactory accuracy and repeatability.
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Desenho de Equipamento/métodos , Imobilização/instrumentação , Extremidade Inferior , Neoplasias/radioterapia , Planejamento da Radioterapia Assistida por Computador , Erros de Configuração em Radioterapia/prevenção & controle , Adulto , China , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imobilização/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias/classificação , Posicionamento do Paciente/instrumentação , Posicionamento do Paciente/métodos , Planejamento da Radioterapia Assistida por Computador/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Reprodutibilidade dos TestesRESUMO
We aim to investigate the effects of adipose-derived stem cells (ASCs) transplantation on irradiation-induced skeletal muscle fibrosis. Sixty-four rabbits were randomly divided into ASCs group and PBS group followed by irradiation at unilateral hip with a single dose of 80 Gy. Nonirradiated side with normal skeletal muscle served as normal control. Skeletal muscle tissues were collected from eight rabbits in each group at 1 w, 4 w, 8 w, and 26 w after irradiation. Migration of ASCs was observed in the peripheral tissues along the needle passage in the injured muscle. The proportion of the area of collagen fibers to the total area in sections of ASCs group was lower than those of PBS groups at 4 w, 8 w, and 26 w after irradiation. Significant decrease was noted in the integrated optimal density of the transforming growth factor ß1 (TGF-ß1) in the ASCs group compared with those of PBS group at 4 w, 8 w, and 26 w after irradiation. Moreover, the expression of TGF-ß1 was lower in the ASCs group compared to those of the PBS group at each time point determined by Western blot analysis. ASCs transplantation could alleviate irradiation fibrosis by suppressing the level of TGF-ß1 in the irradiated skeletal muscle.
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OBJECTIVE: To explore the function of the default mode network (DMN) in the psychopathological mechanisms of theory of mind deficits in patients with an esophageal cancer concomitant with depression in resting the state. SUBJECTS AND METHODS: Twenty-five cases of esophageal cancer with theory of mind deficits (test group) that meet the diagnostic criteria of esophageal cancer and neuropsychological tests, including Beck depression inventory, reading the mind in the eyes, and Faux pas, were included, Another 25 cases of esophageal cancer patients but without theory of mind deficits (control group) were enrolled. Each patient completed a resting-state functional magnetic resonance imaging. RESULTS: The functional connectivity intensities within the cerebral regions in the DMN of all the enrolled patients were analyzed. The results of each group were compared. The functional connectivity of the bilateral prefrontal central region with the precuneus, bilateral posterior cingulate gyrus and bilateral ventral anterior cingulate gyrus in the patients of the test group were all reduced significantly (P < 0.05). In the resting state, the functional connectivity is abnormal in the cerebral regions in the DMN of esophageal cancer patients with theory of mind deficits. CONCLUSIONS: The theory of mind deficits might have an important function in the pathogenesis of esophageal cancer.
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Encéfalo/fisiologia , Neoplasias Esofágicas/psicologia , Descanso/psicologia , Teoria da Mente/fisiologia , Adulto , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
BACKGROUND: To investigate the relationship between pathologic tumor response to concurrent chemo- radiotherapy and variation of serum VEGF in patients with esophageal cancer. MATERIALS AND METHODS: Forty six patients with esophageal cancer who were treated with concurrent chemo-radiotherapy were enrolled. Endoscopic and pathologic examination was conducted before and four weeks afterwards. Serum level of VEGF was documented before, four weeks later and after chemo-radiotherapy. The relationship between pathologic response and the variation of serum level of VEGF and its influence on the prognosis were investigated. RESULTS: Serum level of VEGF decreased remarkably during and after chemo-radiotherapy in patients whose pathologic response was severe (F=5.393, 4.587, P(0.05). There were no statistical differences of serum VEGF level before, during and after chemo-radiotherapy for patients whose pathologic response was moderate or mild. There were 18 (85.7%), 7 (53.8%) and 6 patients (50.0%) whose serum VEGF level dropped in the severe, moderate and mild group, respectively, with significant differences among these groups (p=0.046). Two year survival rates of patients with severe, moderate and mild pathologic response were 61.9%, 53.8% and 33.3% respectively, and no statistically difference between severe and mild group regarding OS (p=0.245) was tested. CONCLUSIONS: Tumor pathologic response during chemo-radiotherapy and the changes of serum VEGF lever could predict curative effects of chemo-radiotherapy in patients with esophageal cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Medular/patologia , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Neoplasias Esofágicas/patologia , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Medular/sangue , Carcinoma Medular/mortalidade , Carcinoma Medular/terapia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Cisplatino/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Prognóstico , Taxa de SobrevidaRESUMO
OBJECTIVE: To study the cancer stem cell populations in esophageal cancer cell lines KYSE150 and TE1 and identify whether resulting stem-like cell spheres display radiation resistance characteristics. METHODS: Serum-free medium (SFM) suspension was used to culture the esophageal cancer stem cell lines and enrich the esophageal stem-like cell spheres. RT-PCR assay was used to detect the stem cell gene expression in the sphere cells. Radiosensitivity of the sphere cells and parental cells were evaluated by clone formation assay. Different cells after irradiation at different doses were tested to evaluate the changes of sphere formation, and cell cycle and CD44(+)CD271(+) expression of the sphere cells were also analyzed by flow cytometry before and after irradiation. RESULTS: Cancer stem-like cell spheres were generated from KYSE150 and TE1 cells and enriched by culture in serum-free medium, and the number of spheres was increasing alone with the increase of cell passages. The numbers of spheres formed from the 1st, 2nd and 3rd generations of KYSE150 cells were 25 ± 2, 37 ± 2 and 47 ± 3, respectively. The numbers of spheres formed from the 1st, 2nd and 3rd generations of TE1 cells were 15 ± 3, 24 ± 3 and 36 ± 4, respectively. Certain doses of radiation increased the sphere formation rate. The average survival fraction (SF2) of the suspension-cultured KYSE150 stem-like cell spheres after 2 Gy irradiation were 0.81 ± 0.03 and 0.69 ± 0.04, while that of TE1 parental cells were 0.87 ± 0.01 and 0.80 ± 0.03 (P < 0.05 for all). In the esophageal parental KYSE150 and TE1 cells, arrest at G2 phase was induced after irradiation. After the same dose of irradiation, the inhibition of proliferation of the cancer stem cells was lower than that of the parent cells (P < 0.05). After 0, 4 and 8 Gy irradiation, the CD44(+)CD271(+) cell percentage of KYSE150 parental cells were (1.08 ± 0.03)%, (1.29 ± 0.07)% and (1.11 ± 0.09)%; the CD44(+)CD271(+) cell percentage of TE1 parental cells were (1.16 ± 0.11)%, (0.97 ± 0.08)% and (1.45 ± 0.35)% (P > 0.05 for all). After 0, 4 and 8 Gy irradiation, the percentage of CD44(+)CD271(+) cells of KYSE150 stem cell-like spheres were (35.83 ± 1.23)%, (44.90 ± 1.67)% and (57.77 ± 1.88)%, and that of TE1 stem cell-like spheres were (16.07 ± 0.91)%, (22.67 ± 1.12)% and (33.27 ± 1.07)%. Compared the 4 Gy and 8 Gy irradiated KYSE150 and TE1 stem-like cell spheres with the 0 Gy irradiated spheres, the differences were statistically significant (P < 0.05 for all). CONCLUSIONS: The cancer stem cells in KYSE150 and TE1 spheres are more radio-resistant than their parental cells. It may suggest that cancer stem cell populations in the esophageal cancer cells are related to the mechanism of occurrence of radioresistance.
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Linhagem Celular Tumoral/diagnóstico por imagem , Neoplasias Esofágicas/diagnóstico por imagem , Células-Tronco Neoplásicas/diagnóstico por imagem , Ciclo Celular , Células Clonais , Citometria de Fluxo , Humanos , Tolerância a Radiação , RadiografiaRESUMO
AIM: To investigate the short-term efficacy and tolerability of radiotherapy plus thalidomide in patients with esophageal cancer (EC). METHODS: Serum samples from 86 EC patients were collected before, during, and after radiotherapy, and the vascular endothelial growth factor (VEGF) level was examined by ELISA. According to the change in serum VEGF level during radiotherapy, the patients were divided into two groups: in the drug group, VEGF level was increased or remained unchanged, and thalidomide was administered up to the end of radiotherapy; in the non-drug group, VEGF level was decreased and radiotherapy was given alone. Thirty healthy volunteers served as controls. The efficacy and safety of radiotherapy plus thalidomide therapy were investigated. RESULTS: The 86 EC patients had a significantly higher level of VEGF compared with the 30 healthy controls before radiotherapy (P < 0.01), and the VEGF level was significantly correlated with primary tumor size, lymph node metastasis, histopathologic type, and clinical stage (P < 0.01). Of 83 evaluable cases, VEGF level was significantly decreased after radiotherapy in 32 patients in the drug group (P < 0.05), with an effective rate of 71.88%. The incidence of dizziness and/or burnout in the drug group and non-drug group was 62.50% and 15.69%, respectively (P = 0.000), and the incidence of somnolence was 12.50% and 0%, respectively (P = 0.019). No significant differences were observed. CONCLUSION: Thalidomide can down-regulate serum VEGF level in EC patients, and combined with radiotherapy may improve treatment outcome. Thalidomide was well tolerated by EC patients.
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Inibidores da Angiogênese/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Talidomida/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Biomarcadores/sangue , Quimiorradioterapia/efeitos adversos , China , Regulação para Baixo , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Talidomida/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
The repairing function and differentiation potency of adipose stem cells (ASCs) transplantation following skeletal muscle injury induced by radiotherapy are still not well defined. In this study, one side of the buttocks of 64 New Zealand white rabbits underwent irradiation and were randomly divided into an ASCs group [5×10(7) ASCs labeled with CM-Dil and suspended in 1 mL of phosphate-buffered saline (PBS), via intramuscular injection] and a PBS group (1 mL of PBS, via intramuascular injection). ASCs were isolated in New Zealand white rabbits in vitro, and migration of ASCs labeled with CM-Dil was observed after transplantation in vivo. A significant decrease of histological severity scoring was found in irradiated tissue obtained in the ASCs group compared with that in PBS group. Additionally, compensatory hyperplasia was noted after ASCs transplantation in the injured tissues. Moreover, ASCs could upregulate the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and promote the angiogenesis of the injured tissues. Interestingly, myofilament-like structures were identified in irradiated muscle cells after ASCs transplantation. We concluded that ASCs transplantation could repair the radiation-induced skeletal muscle injury. Its mechanism may be, at least partly, associated with the upregulation of VEGF and bFGF, angiogenesis, promoting the compensatory hyperplasia of muscle satellite cells, as well as the myogenic differentiation.
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Adipócitos/metabolismo , Músculo Esquelético/lesões , Músculo Esquelético/metabolismo , Lesões Experimentais por Radiação/terapia , Transplante de Células-Tronco , Células-Tronco/metabolismo , Adipócitos/citologia , Adipócitos/transplante , Aloenxertos , Animais , Músculo Esquelético/patologia , Coelhos , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Regeneração , Células-Tronco/patologiaRESUMO
AIM: To study the cancer stem cell population in esophageal cancer cell lines KYSE-150 and TE-1 and identify whether the resulting stem-like spheroid cells display cancer stem cells and radiation resistance characteristics. METHODS: A serum-free medium (SFM) suspension was used to culture esophageal cancer stem cell lines and enrich the esophageal stem-like spheres. A reverse transcription polymerase chain reaction assay was used to detect stem cell gene expression in the spheroid cells. Radiosensitivity of stem-like spheres and parental cells were evaluated by clonogenic assays. Furthermore, different cells after different doses of irradiation were tested to evaluate the change in sphere formation, cell cycle and CD44(+)CD271(+) expression of tumor stem-like spheroid cells using flow cytometry before and after irradiation. RESULTS: The cells were observed to generate an increased number of spheres in SFM with increasing cell passage. Radiation increased the rate of generation of stem-like spheres in both types of cells. The average survival fraction (SF2) of the cultured KYSE-150 compared with TE-1 stem-like spheres after 2 Gy of radiation was 0.81 ± 0.03 vs 0.87 ± 0.01 (P < 0.05), while the average SF2 of KYSE-150 compared with TE-1 parental cells was 0.69 ± 0.04 vs 0.80 ± 0.03, P < 0.05. In the esophageal parental cells, irradiation dose-dependently induced G2 arrest. Stem-like esophageal spheres were resistant to irradiation-induced G2 arrest without significant changes in the percentage population of irradiated stem-like cells. Under irradiation at 0, 4, and 8 Gy, the CD44(+)CD271(+) cell percentage for KYSE150 parental cells was 1.08% ± 0.03% vs 1.29% ± 0.07% vs 1.11% ± 0.09%, respectively; the CD44(+)CD271(+) cell percentage for TE1 parental cells was 1.16% ± 0.11% vs 0.97% ± 0.08% vs 1.45% ± 0.35%, respectively. The differences were not statistically significant. Under irradiation at 0, 4, and 8 Gy, the CD44(+)CD271(+) cell percentage for KYSE-150 stem-like spheres was 35.83% ± 1.23% vs 44.9% ± 1.67% vs 57.77% ± 1.88%, respectively; the CD44(+)CD271(+) cell percentage for TE1 stem-like spheres was 16.07% ± 0.91% vs 22.67% ± 1.12%, 16.07% ± 0.91% vs 33.27% ± 1.07%, respectively. The 4 and 8 Gy irradiated KYSE-150 and TE-1 stem-like spheres were compared with the 0 Gy irradiated group, and the differences were statistically significant (P < 0.05). CONCLUSION: The KYSE-150 and TE-1 stem-like spheres are more radioresistant than their parental cells which may suggest that cancer stem cells are related to radioresistance.
Assuntos
Neoplasias Esofágicas/radioterapia , Células-Tronco Neoplásicas/efeitos da radiação , Tolerância a Radiação , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Relação Dose-Resposta à Radiação , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Citometria de Fluxo , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Células-Tronco Neoplásicas/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esferoides Celulares , Fatores de TempoRESUMO
AIM: To characterize the two components of theory of mind (ToM) in patients with esophageal cancer combined with depression. METHODS: Sixty-five patients with esophageal cancer combined with depression (depressed group) and 62 normal controls (control group) were assessed using reading the mind in the eyes test, faux pas task, verbal fluency test, digit span test and WAIS IQ test. The depressed group was divided into two subgroups including psychotic depressed (PD) group (32 cases) and nonpsychotic depressed (NPD) group (33 cases). The clinical symptoms of patients were assessed using Beck depression inventory versionâ IIâ and brief psychiatric reacting scale (BPRS). RESULTS: There was a significant difference between the depressed group and the control group on tasks involving ToM social perceptual components (mind reading: t = 7.39, P < 0.01) and tests involving ToM social cognitive components (faux pas questions: t = 13.75, P < 0.01), respectively. A significant difference was also found among the PD group, the NPD group and the control group on mind reading (F = 32.98, P < 0.01) and faux pas questions (χ² = 78.15, P < 0.01), respectively. The PD group and NPD group performed worse than normal group controls both on mind reading and faux pas questions (P < 0.05). The PD group performed significantly worse than the NPD group on tasks involving ToM (mind reading: F = 18.99, P < 0.01; faux pas questions: F = 36.01, P < 0.01). In the depressed group, there was a negative correlation between ToM performances and BPRS total score (mind reading: r = -0.35, P < 0.01; faux pas questions: r = -0.51, P < 0.01), and between ToM performances and hostile suspiciousness factor score (mind reading: r = -0.75, P < 0.01; faux pas questions: r = -0.73, P < 0.01), respectively. CONCLUSION: The two components of ToM are both impaired in patients with esophageal cancer combined with depression. This indicates that there may be an association between ToM deficits and psychotic symptoms in clinical depression.
Assuntos
Depressão/psicologia , Neoplasias Esofágicas/psicologia , Teoria da Mente , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Cognição , Depressão/complicações , Depressão/diagnóstico , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Percepção , Escalas de Graduação Psiquiátrica , Comportamento SocialRESUMO
The purposes of this study were to test the effect of tetrandrine, alone or combined with radiation, on human esophageal cancer cell line TE1 (TE1 cells) and investigate the potential antitumor mechanism. Human esophageal cancer cell line TE1 was tested by methyl thiazolyl tetrazolium assay for cell proliferation, colony-forming assay for cell radiosensitivity, flow cytometry assay for cell cycle distribution, and western blot assay for cell cycle protein expression. When treated alone, tetrandrine had a time- and concentration-dependent cytotoxic effect on TE1 cells. The dose-enhancement ratio for combined tetrandrine and radiation was markedly increased when compared with tetrandrine alone. Further, expression of cyclin B1 protein increased after addition of tetrandrine when compared with radiation only. Radiation-induced G2 arrest was abrogated with treatment of tetrandrine. In conclusion, tetrandrine can enhance the radiosensitivity of TE1 cells and this may involve relief of radiation-induced G2/M arrest in TE1 cells.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Benzilisoquinolinas/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Radiossensibilizantes/farmacologia , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Processos de Crescimento Celular/efeitos dos fármacos , Processos de Crescimento Celular/efeitos da radiação , Linhagem Celular Tumoral , Terapia Combinada , Ciclina B1/biossíntese , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Humanos , Tolerância a Radiação/efeitos dos fármacosRESUMO
To investigate the effects of thalidomide on the radiosensitivity of human esophageal cancer cells (TE1 cells) and the potential mechanism underlying these effects. The effects of thalidomide on proliferation of TE1 cells were determined by Methyl thiazolyl tetrazolium assay. The multitarget click model was used to delineate the survival curve using a colony-forming assay, and the radiosensitivity was determined after TE1 cells were treated by thalidomide and/or X-ray radiation. The cell cycle was detected using flow cytometry. Our results are as follows: thalidomide alone suppressed the proliferation of TE1 cells in a dose- and time-dependent manner. The suppressive effects were enhanced by prolonged duration or elevated concentration of thalidomide. However, thalidomide did not affect the cell cycle of TE1 cells. The expression of vascular endothelial growth factor (VEGF) mRNA and protein was suppressed after treatment with thalidomide alone in a dose-dependent manner. Synergistic suppressive effects on VEGF expression were observed after administration of thalidomide and X-ray exposure. In conclusion, thalidomide was able to enhance the radiosensitivity of TE1 cells in vitro, which could be closely related to its suppressive effects on the expression of VEGF in TE1 cells, but had no obvious effects on the cell cycle.
Assuntos
Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Talidomida/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Processos de Crescimento Celular/efeitos dos fármacos , Processos de Crescimento Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Terapia Combinada , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Raios XRESUMO
OBJECTIVE: To observe the clinical effectiveness and safety of Tiantai No. 1 (TT1) in treating mild cognitive impairment (MCI). METHODS: With randomized double-blinded method adopted, the 128 MCI patients, selected according to the commonly accepted standard for MCI diagnosis, were assigned to 2 groups, the treatment group (65 cases) treated with TT1 and the control group (63 cases) treated with placebo for six months. Besides, a normal control group with 30 healthy elders was set up. Changes of comprehensive cognitive function, instant memory, short-term memory, calculation ability, orientating ability of time and space, language understanding ability as well as Chinese medicine syndromes before and after treatment were observed and compared. RESULTS: The cognitive function of MCI patients was significantly lower than that of healthy elders (P<0.01). The comprehensive cognitive function, and all the above-mentioned abilities were significantly improved (P<0.05, P<0.01) in the TT1 treated group after treatment, with an effect significantly better than that in the placebo treated group (P<0.01). Overall evaluation of effect and safety suggested that the clinical effectiveness index (CEI) of TT1 was notably higher than that of the placebo. And it was found in one-year follow-up that the incidence of developing to Alzheimer's disease (AD) in the treatment group was strikingly lower than that in the control group (P<0.01). CONCLUSION: TT1 can significantly improve the cognitive function of MCI patients, and reduce their incidence of developing to AD.